Pyrethroids are the major insecticides used to control populations of Culex pipiens s.l. mosquitoes in the USA and Africa. Resistance to pyrethroids is emerging in populations of these mosquitoes, where they are vectors of West Nile virus in the USA and Rift Valley fever virus and Bancroftian filariasis in Africa. Direct evidence strongly suggests that this resistance is mediated by enzymatic detoxification including Glutathione S Transferases (GSTs). The goal of this research is therefore to isolate those GST isozymes responsible for mediating resistance for the purpose of developing assays for diagnosing the status of resistance. To achieve the stated goal the following aims will be pursued; Aim #1. Generate separate adult and larval pyrethroid resistant strains of Culex pipiens complex mosquitoes Aim #2. Purify and obtain amino acid sequence of GSTs that conjugate glutathione to pyrethroids Aim #3. Clone and express GST isozymes using a bacterial expression system Aim #4. Develop GST based diagnostic assays for pyrethroid resistance Once these GST isozymes are identified and assays developed they can be used in resistance monitoring and mitigation and management strategies to prolong the effective use of pyrethroids. These studies will also lead to understanding the mechanism of metabolic resistance to aid in development of novel, next generation insecticides and synergists that may augment pyrethroids. [unreadable] [unreadable] [unreadable]